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首页> 外文期刊>Molecular and Cellular Biology >Mind bomb-1 Is Essential for Intraembryonic Hematopoiesis in the Aortic Endothelium and the Subaortic Patches
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Mind bomb-1 Is Essential for Intraembryonic Hematopoiesis in the Aortic Endothelium and the Subaortic Patches

机译:头脑炸弹1对于主动脉内皮和主动脉下斑块的胚内造血至关重要

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Intraembryonic hematopoiesis occurs at two different sites, the floor of the aorta and subaortic patches (SAPs) of the para-aortic splanchnopleura (P-Sp)/aorta-gonad-mesonephros (AGM) region. Notch1 and RBP-jκ are critical for the specification of hematopoietic stem cells (HSCs) in Notch signal-receiving cells. However, the mechanism by which Notch signaling is triggered from the Notch signal-sending cells to support embryonic hematopoiesis remains to be determined. We previously reported that Mind bomb-1 (Mib1) regulates Notch ligands in the Notch signal-sending cells (B. K. Koo, M. J. Yoon, K. J. Yoon, S. K. Im, Y. Y. Kim, C. H. Kim, P. G. Suh, Y. N. Jan, and Y. Y. Kong, PLoS ONE >2:e1221, 2007). Here, we show that intraembryonic hematopoietic progenitors were absent in the P-Sp of Mib1?/? embryos, whereas they were partly preserved in the Tie2-cre; Mib1f/f P-Sps, suggesting that Mib1 plays a role in the endothelium and the SAPs. Interestingly, dll1 and dll4/Jag1 are expressed in the SAPs and the endothelium of the AGM, respectively, where mib1 is detected. Indeed, Notch signaling was activated in the nascent HSCs at both sites. In the P-Sp explant culture, the overexpression of Dll1 in OP9 stromal cells rescued the failed production of hematopoietic progenitors in the Mib1?/? P-Sp, while its activity was abolished by Mib1 knockdown. These results suggest that Mib1 is important for intraembryonic hematopoiesis not only in the aortic endothelium but also in the SAPs.
机译:胚内造血发生在两个不同的部位,主动脉底和主动脉副内脏(P-Sp)/主动脉-性腺-中肾(AGM)区域的主动脉下膜(SAP)。 Notch1和RBP-jκ对于Notch信号接收细胞中的造血干细胞(HSC)的规范至关重要。然而,从Notch信号发送细胞触发Notch信号以支持胚胎造血的机制仍有待确定。我们先前曾报道Mind bomb-1(Mib1)调节Notch信号发送细胞中的Notch配体(BK Koo,MJ Yoon,KJ Yoon,SK Im,YY Kim,CH Kim,PG Suh,YN Jan和YY Kong, PLoS ONE > 2: e1221,2007)。在这里,我们显示 Mib1 ?/?胚胎的P-Sp中不存在胚内造血祖细胞,而部分保留在 Tie2-cre < / em>; Mib1 f / f P-Sps,表明Mib1在内皮和SAP。有趣的是, dll1 dll4 / Jag1 分别在SAP和AGM的内皮中表达,其中 mib1 被检测到。实际上,在两个部位的新生HSC中均激活了Notch信号传导。在P-Sp外植体培养物中,OP9基质细胞中Dll1的过表达挽救了 Mib1 ?/? P-Sp中造血祖细胞的失败生产,但其活性被Mib1淘汰赛废除了。这些结果表明,Mib1对于胚胎内造血不仅在主动脉内皮中而且在SAP中都很重要。

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